Dataset Information

Prolonged electromechanical delay as an early predictor of trastuzumab-induced cardiotoxicity in patients undergoing treatment for breast cancer.

ABSTRACT:

Background

We aimed to investigate if left ventricular electromechanical delay (LVEMD) prolongation predicts trastuzumab-induced cardiotoxicity (TIC) in breast cancer patients.

Hypothesis

LVEMD prolongation on serial echocardiograms could be an indicator of subclinical TIC.

Methods

We included 237 breast cancer patients receiving trastuzumab chemotherapy, who underwent echocardiography at baseline and at 6 and 12 months after trastuzumab initiation. LVEMD was defined as the time from electrical activation to myocardial contraction. TIC was defined as left ventricular ejection fraction (LVEF) worsening to <55%, either as symptomatic decrease of ≥5% or asymptomatic decrease of ≥10%.

Results

During a mean follow-up of 547 days, TIC occurred in 27 patients (11.4%). Changes in the time intervals from QRS onset on electrocardiography to the beginning and peak of transaortic flow on pulsed-wave Doppler echocardiography (ie, ΔLVEMDi and ΔLVEMDp, respectively) were independent predictors of TIC. On receiver operating characteristic curve analysis, the optimal cutoff value for TIC prediction was 23 milliseconds for ΔLVEMDi (sensitivity, 0.85; specificity, 0.78; area under the curve [AUC], 0.882) and 21 milliseconds for ΔLVEMDp (sensitivity, 0.96; specificity, 0.68; AUC, 0.860). The C-index for TIC prediction increased significantly after adding ΔLVEMDi and ΔLVEMDp to conventional models that included clinical variables, baseline LVEF, and changes in global longitudinal peak systolic strain. Similarly, adding ΔLVEMDi or ΔLVEMDp to conventional models provided significant improvement in discrimination capability for TIC prediction (integrated discrimination improvement and continuous net reclassification improvement index).

Conclusion

ΔLVEMDi and ΔLVEMDp may serve as predictors of subclinical cardiac dysfunction in breast cancer patients receiving trastuzumab.

SUBMITTER: Choe JC

PROVIDER: S-EPMC6489867 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Publications

Prolonged electromechanical delay as an early predictor of trastuzumab-induced cardiotoxicity in patients undergoing treatment for breast cancer.

Choe Jeong Cheon JC Choi Jung Hyun JH Choi Jong Hyun JH Ahn Jinhee J Park Jin Sup JS Lee Hye Won HW Oh Jun-Hyok JH Lee Han Cheol HC Cha Kwang Soo KS Hong Taek Jong TJ

Clinical cardiology 20181016 10

<h4>Background</h4>We aimed to investigate if left ventricular electromechanical delay (LVEMD) prolongation predicts trastuzumab-induced cardiotoxicity (TIC) in breast cancer patients.<h4>Hypothesis</h4>LVEMD prolongation on serial echocardiograms could be an indicator of subclinical TIC.<h4>Methods</h4>We included 237 breast cancer patients receiving trastuzumab chemotherapy, who underwent echocardiography at baseline and at 6 and 12 months after trastuzumab initiation. LVEMD was defined as the ...[more]

PMID: 30239009

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Project description:BackgroundTrastuzumab is used, alone or in conjunction with standard chemotherapy, to treat HER2-positive breast cancer (BC). Although it improves cancer outcomes, trastuzumab. can lead to cardiotoxicity. Physical exercise is a safe and effective supportive therapy in the management of side effects, but the cardioprotective effects of exercise are still unclear.ObjectivesThe primary aim of this study was to test whether trastuzumab-induced cardiotoxicity [left ventricular ejection fraction (LVEF) under 50%, or an absolute drop in LVEF of 10%] was reduced after a supervised exercise program of 3 months in patients with HER2-positive breast cancer. Secondary endpoints were to evaluate (i) cardiotoxicity rates using other criteria, (ii) cardiac parameters, (iii) cardiorespiratory fitness and (iv) whether a change in LVEF influences the cardiorespiratory fitness.Methods89 women were randomized to receive adjuvant trastuzumab in combination with a training program (training group: TG; n = 46) or trastuzumab alone (control group: CG; n = 43). The primary and secondary endpoints were evaluated at the end of the supervised exercise program of 3 months (T3).ResultsAfter exercise program, 90.5 % of TG patients and 81.8% of CG patients did not exhibit cardiotoxicity. Furthermore, whatever the used criterion, percentage of patients without cardiotoxicity were greater in TG (97.6 and 100% respectively) than in CG (90.9 and 93.9% respectively). LVEF and GLS values remained stable in both groups without any difference between the groups. In contrast, at T3, peak VO2 (+2.6 mL.min-1.kg-1; 95%CI, 1.8 to 3.4) and maximal power (+21.3 W; 95%CI, 17.3 to 25.3) increased significantly in TG, whereas they were unchanged in CG (peak VO2: +0.2 mL.min-1.kg-1; 95%CI, -0.5 to 0.9 and maximal power: +0.7 W, 95%CI, -3.6 to 5.1) compared to values measured at T0. No correlation between LVEF changes and peak VO2 or maximal power was observed.ConclusionA 12-week supervised exercise regimen was safe and improved the cardiopulmonary fitness in particular peak VO2, in HER2-positive BC patients treated with adjuvant trastuzumab therapy. The study is under powered to come to any conclusion regarding the effect on cardiotoxicity.Clinical trial registrationwww.ClinicalTrials.gov, identifier: NCT02433067.

Project description:BackgroundThe use of trastuzumab has proven to be a successful strategy in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer; however, it is associated with an increased risk of cardiac dysfunction. We performed an up-to-date, comprehensive meta-analysis to clarify the risk of congestive heart failure (CHF) in patients with early breast cancer receiving different durations of adjuvant trastuzumab with the longest-term follow-up.MethodsEligible studies included randomized control trials of HER2-positive early breast cancer patients with or without trastuzumab in adjuvant chemotherapy. Adequate reporting of CHF data were required for inclusion. Statistical analyses were conducted to calculate the overall incidence, relative risk (RR), and 95% confidence interval (CI) by use of a fixed-effects model.ResultsSix randomized control trials including 18,111 patients were identified. The overall incidence of high-grade CHF in patients treated with trastuzumab versus placebo was 1.44% (95% CI, 0.79%-2.64%) and the RR was 3.19 (95% CI, 2.03-5.02; p < .00001). In subgroup analysis, the difference in CHF incidence failed to achieve significance. The RR for 8 mg/kg trastuzumab (high dose) was greater than that for 4 mg/kg (low dose) (RR, 6.79, 95% CI, 2.03-22.72, p = .0001; versus RR, 2.64; 95% CI, 1.61-4.32; p = .002). Additionally, higher RRs were observed for patients receiving trastuzumab for 1 year (RR, 3.29; 95% CI, 2.07-5.25) and 2 years (RR, 9.54; 95%CI, 2.19-41.43), but not 9 weeks (RR, 0.50; 95% CI, 0.05-5.49) compared with control groups. No evidence of publication bias was observed.ConclusionAdjuvant trastuzumab therapy was strongly associated with an increased risk of significant CHF in patients with early breast cancer, particularly in 2-year use.Implications for practiceThis comprehensive meta-analysis evaluated the risk of congestive heart failure with a usage profile of adjuvant trastuzumab in patients with early breast cancer. Before initiating treatment with trastuzumab, a risk-benefit analysis for individual patients should be critically evaluated, considering that the prognosis is closely related to drug dose and duration of use. Cardiac function should be monitored throughout the treatment period and also during follow-up. Thus, early identification of trastuzumab-related cardiac dysfunction can allow effective medical intervention, elimination of symptoms, recovery of function, and continuation of trastuzumab therapy.

Project description:BackgroundIn patients treated with cardiotoxic chemotherapies, the presence of cardiovascular risk factors and previous cardiac disease have been strongly correlated to the onset of cardiotoxicity. The influence of overweight and obesity as risk factors in the development of treatment-related cardiotoxicity in breast cancer (BC) was recently suggested. However, due to meta-analysis design, it was not possible to take into account associated cardiac risk factors or other classic risk factors for anthracycline (antineoplastic antibiotic) and trastuzumab (monoclonal antibody) cardiotoxicity.Methods and findingsUsing prospective data collected from 2012-2014 in the French national multicenter prospective CANTO (CANcer TOxicities) study of 26 French cancer centers, we aimed to examine the association of body mass index (BMI) and cardiotoxicity (defined as a reduction in left ventricular ejection fraction [LVEF] > 10 percentage points from baseline to LVEF < 50%). In total, 929 patients with stage I-III BC (mean age 52 ± 11 years, mean BMI 25.6 ± 5.1 kg/m2, 42% with 1 or more cardiovascular risk factors) treated with anthracycline (86% epirubicin, 7% doxorubicin) and/or trastuzumab (36%), with LVEF measurement at baseline and at least 1 assessment post-chemotherapy were eligible in this interim analysis. We analyzed associations between BMI and cardiotoxicity using multivariate logistic regression. At baseline, nearly 50% of the study population was overweight or obese. During a mean follow-up of 22 ± 2 months following treatment completion, cardiotoxicity occurred in 29 patients (3.2%). The obese group was more prone to cardiotoxicity than the normal-weight group (9/171 versus 8/466; p = 0.01). In multivariate analysis, obesity (odds ratio [OR] 3.02; 95% CI 1.10-8.25; p = 0.03) and administration of trastuzumab (OR 12.12; 95% CI 3.6-40.4; p < 0.001) were independently associated with cardiotoxicity. Selection bias and relatively short follow-up are potential limitations of this national multicenter observational cohort.ConclusionsIn BC patients, obesity appears to be associated with an important increase in risk-related cardiotoxicity (CANTO, ClinicalTrials.gov registry ID: NCT01993498).Trial registrationClinicalTrials.gov NCT01993498.

Project description:BackgroundClinical trials have demonstrated an increased risk of cardiotoxicity in patients with breast cancer (bca) receiving trastuzumab-based therapy. Diabetes, dyslipidemia, and obesity are known risk factors for cardiovascular disease. Studies have yielded conflicting results about whether those factors increase the risk of cardiotoxicity in patients with bca receiving trastuzumab.MethodsIn this retrospective cohort study, data were collected for 243 patients with bca positive for her2 (the human epidermal growth factor receptor 2) who were receiving trastuzumab and who were referred to The Ottawa Hospital Cardio-oncology Referral Clinic between 2008 and 2013. The data collected included patient demographics, reason for referral, cardiac function, chemotherapy regimen (including anthracycline use), and 3 comorbidities (diabetes, dyslipidemia, obesity). Rates of symptomatic cancer treatment-related cardiac dysfunction (sctcd) and asymptomatic decline in left ventricular ejection fraction (adlvef) were calculated for patients with and without the comorbidities of interest.ResultsOf the 243 identified patients, 104 had either diabetes, dyslipidemia, or obesity. In that population, the most likely reason for referral to the cardio-oncology clinic was adlvef. The combination of 2 or 3 comorbidities significantly increased the incidence of sctcd in our population, reaching a rate of 67% for patients with obesity and dyslipidemia [relative risk (rr): 2.2; p = 0.04], 69% for patients with obesity and diabetes (rr: 2.3; p = 0.02), and 72% for patients with all 3 risk factors (rr: 2.4; p = 0.08).ConclusionsThe combination of 2 or 3 comorbidities significantly increases the incidence of symptomatic cancer treatment-related cardiotoxicity. Patients with bca experiencing cancer treatment-related cardiotoxicity who have a history of diabetes, dyslipidemia, and obesity might require more proactive strategies for prevention, detection, and treatment of cardiotoxicity while receiving trastuzumab-based treatment.

Dataset Information

Prolonged electromechanical delay as an early predictor of trastuzumab-induced cardiotoxicity in patients undergoing treatment for breast cancer.

Background

Hypothesis

Methods

Results

Conclusion

Publications

Prolonged electromechanical delay as an early predictor of trastuzumab-induced cardiotoxicity in patients undergoing treatment for breast cancer.

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